Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic, n-decanoic, n-heptanoic, and n-octanoic acids

Endpoint summary

Description of key information

Skin irritation/corrosion: not irritating (OECD 404, GLP, analogue approach)
Eye irritation: not irritating (OECD 405, GLP, analogue approach)

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the polyol esters family will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the polyol esters family will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

Justification for grouping of substances and read-across

There are no data available on the skin and eye irritation potential of the substance Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1). In order to fulfil the standard information requirements set out in Annex VIII, 8.2, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests", which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby toxicological properties may be predicted from data for the reference substance(s) on the basis of structural similarity, the substances listed below are selected as reference substances for assessment of toxicological endpoints, for which information gaps are identified.

Overview for skin and eye irritation/corrosion

CAS	Skin Irritation/Corrosion	Eye Irritation/Corrosion
70983-72-1 (a) Target substance	RA: CAS 68424-31-7 RA: CAS 84418-63-3 RA: CAS 131459-39-7	Not corrosive, slight irritating potential RA: CAS 68424-31-7 RA: CAS 84418-63-3 RA: CAS 131459-39-7
84418-63-3 (b)	Not irritating	Not irritating
68424-31-7	Not irritating	Not irritating
131459-39-7	Not irritating	Not irritating

 (a) Substances subject to the REACh  Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

        (b) Substances that are either already registered under REACh or not subject to the REACh  Phase-in registration deadline of       31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

 

The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Skin Irritation

Since no animal studies investigating the skin irritation potential of Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substances Fatty acids, C5-10 mixed esters with pentaerythritol (CAS# 68424-31-7), Isononanoic acid, mixed esters with dipentaerythritol, heptanoic acid and pentaerythritol (CAS# 84418-63-3), 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS# 131459-39-7), was conducted.

Skin irritation - Animal Data

Several structurally related analogue substances were tested in vivo on rabbit skin. All study results indicated no skin irritation potential.

CAS 68424-31-7

Three primary skin irritation studies were conducted to assess the skin irritation potential of Fatty acids, C5-10 mixed esters with pentaerythritol (CAS# 68424-31-7).

In the first primary skin irritation study comparable to OECD Guideline 404 (Croda, 1991a) the shaved skin of 3 female New Zealand White rabbits was exposed to 0.5 mL unchanged test substance for 4 hours under semiocclusive conditions. Skin reactions were assessed according to Directive 67/548/CEE approx. 1, 24, 48, 72 and 96 hours after removal of the test substance. The exposure period of 4 hours caused slight edema (score = 1) in all animals 24 hours after removal of the test substance which was completely reversed within 48 hours. Erythema was seen at the test site of one animal (score = 2) and slight at the test site of the other two animals (score =1). Erythema reactions were completely reversed within 96 hours after removal of the test substance in all three animals. All treated skin sites appeared normal at the 96 hour observation.

 

Two further primary dermal irritation studies were conducted with 0.5 mL test substance on the shaved skin of 3 male New Zealand White rabbits comparable to OECD Guideline 404 (Croda 1991b + c). Skin reactions were assessed according to Draize score 1, 24, 48, 72, 96 hours and 7, 8 and 12 days after removal of the test substance. Following the single 4-hour application in the first study, moderate to severe erythema (maximum score = 4) and moderate to severe edema (maximum score = 4) were observed for 2 or 3 days after application in all animals. This regressed and no signs of erythema or edema were evident 4 to 12 days after application. Thickening of the skin at the application site was seen on one animal between 4 and 7 days after application. No other signs of irritations were observed. For the second study, following the single 4-hour application, very slight to well-defined erythema and very slight to slight oedema were observed in all animals (maximum score = 2). This regressed and no signs of erythema or oedema were evident 11 or 12 days after application. Slight desquamation at the application site of one animal was observed 7 days after application.

 

The test material is not considered irritating to the skin in these studies.

 

CAS 84418-63-3

Isononanoic acid, mixed esters with dipentaerythritol, heptanoic acid and pentaerythritol (CAS# 84418-63-3) was investigated in a primary skin irritation study according to OECD 404 (Croda, 1991). The shaved left flank of the dorso-lumbar region of 3 New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semi-occlusive conditions. After exposure the skin was cleaned from the residual test substance using warm water. The rabbits were observed for 3 days. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48, 72 hours after removal of the test substance. Very slight erythema was observed in all animals 30 - 60 min (2 animals) or 24 h (1 animal) after patch removal. The effects were reversible within 48 h (1 animal) or 72 h (2 animals) respectively. No edema or other irritation effects were observed.

 

CAS 131459-39-7

3,5,5-trimethylhexanoic acid mixed tetraesters with PE and valeric acid (CAS# 131459-39-7) was tested in a primary skin irritation study performed according to OECD Guideline 404 (Croda 1992) under GLP conditions. The shaved dorsal skin of three New Zealand rabbits was exposed to 0.5 mL undiluted test material for 4 hours under semi-occlusive conditions. The rabbits were observed for 7 days. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48, 72 hours as well as 7 days after removal of the test substance. Slight to weak erythema and oedema were observed in all three animals during the first 72 h after exposure. Very slight erythema was noted at all treated skin sites at the 24 and 48-hour observations and at two treated skin sites at the 72-hour observation. Very slight edema was noted at all treated skin sites at the 24-hour observation and persisted at two treated skin site at the 48 and 72-hour observations. Very slight edema was noted at all treated skin sites at the 24-hour observation and persisted at two treated skin site at the 48 and 72-hour observations. However signs of skin irritation reversed within 7 days.

 

Skin irritation - Human Data

Supplementary data is available. A human patch test was conducted using Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1). Only limited reporting is available. The substance was applied undiluted to the back of 11 healthy volunteers for 24 hours (Guibaud, 2004). No skin reactions were observed at the reading time point and the primary skin irritation index was calculated to be 0.

 

In summary, several animal and human studies are available to assess the skin irritation potential of Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1). And there is no indication for a skin irritating potential.

 

Eye irritation

Two in vitro eye irritation studies were conducted with Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1). Although the study results were only given as a short summary, the results are considered adequate in combination with read-across data of the structural analogues substances Fatty acids, C5-10 mixed esters with pentaerythritol (CAS# 68424-31-7) , Isononanoic acid, mixed esters with dipentaerythritol, heptanoic acid and pentaerythritol (CAS# 84418-63-3), 3,5,5-trimethylhexanoic acid mixed tetraesters with PE and valeric acid (CAS# 131459-39-7) in a weight of evidence approach.

 

For both in vitro studies only limited reporting is available. In a HETCAM assay Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1) was tested for its acute eye irritation potential in vitro (Stearinerie, 2004). The chorioallantoic membranes of chicken eggs were exposed to the test substance. The irritation score was reported to be 0. Thus, the test material is not considered corrosive to the eyes in this test but further evaluation regarding irritation potential is necessary.

 

In another in vitro study with limited reporting Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1) was tested for its cytotoxicity in fibroblasts (Stearinerie, 2004). The Ocular Irritation Index in fibroblasts (IOeq) based on cytotoxicity was found to be 8.4. Based on expert judgement the substance is considered to have a slight irritating potential.

 

CAS 68424-31-7

An acute eye irritation study was performed with substances Fatty acids, C5-10 mixed esters with pentaerythritol (CAS# 68424-31-7) according to OECD Guideline 405 (Croda, 1991). 0.1 mL of the undiluted test substance was instilled into the conjunctival sac of one eye of 3 New Zealand White rabbits. The animals were observed for 72 hours. Eye irritation was scored according to the method of Draize 24, 48 and 72 hours after application. No corneal or iridial effects were observed. Conjunctival effects included slight redness (1 animal) and slight discharge (1 animal) and were transiently seen approx. 1 h after dosing.

 

CAS 84418-63-3

Isononanoic acid, mixed esters with dipentaerythritol, heptanoic acid and pentaerythritol (CAS# 84418-63-3) was tested for its eye irritation potential according to OECD Guideline 405 (Croda, 1992). 0.1 mL of the undiluted test substance was instilled into the conjunctival sac of three New Zealand White rabbits. The animals were observed for 72 hours. Eye irritation was scored according to the Draize method 2, 24, 48 and 72 hours after application. No corneal or iris effects were observed. Conjunctival effects included slight redness and slight to moderate discharge. The effects had completely regressed by Day 3. Dried secretions on the upper and lower eyelids were present 1 day after dosing in 1 animal.

 

CAS 131459-39-7

An acute eye irritation study was performed with 3,5,5-trimethylhexanoic acid mixed tetraesters with PE and valeric acid (CAS# 131459-39-7) according to the OECD guideline 405 (Croda, 1999). 0.1 mL of the undiluted test substance was instilled into the conjunctival sac of one eye of 3 New Zealand White rabbits. The animals were observed for 72 hours. Eye irritation was scored according to the Draize method 1, 24, 48 and 72 hours after application. No corneal or irridal effects were noted. Moderate conjunctival irritation was noted in all treated eyes at the 1-hour observation with minimal conjunctival irritation noted in all treated eyes at the 24-hour observation and one treated eye at the 48-hour observation. Treated eyes appeared normal 48 to 72 hours after treatment.

 

Several acute eye irritation studies have been performed in rabbits in vivo. None of the tested structural analogues showed an eye irritation potential. Therefore, based on a weight of evidence approach, no classification for eye irritation for all substances within the Fatty acid methyl esters category is required.

 

Conclusion for skin and eye irritation

In conclusion, data from studies with source substances substances Fatty acids, C5-10 mixed esters with pentaerythritol (CAS# 68424-31-7), Isononanoic acid, mixed esters with dipentaerythritol, heptanoic acid and pentaerythritol (CAS# 84418-63-3), 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS# 131459-39-7), and additional human data do not give an indication that Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1) is considered to be skin irritating.

Eye irritation potential has assessed with data from the same read-across substances. Two in vitro and three in vivo assays did not show an indication of eye irritating potential. Therefore, using structurally related analogue based read-across Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1) is not considered to be eye irritating.

Justification for classification or non-classification

Based on read-across from the structurally similar substances, the available data on skin/eye irritation potential do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.